Endogenous and iatrogenic sources of variability in response to opioid therapy in Post-Surgical and injured orthopedic patients

Hydrocodone is the most prescribed opioid in the US. The objective was to evaluate associations between genetic, intrinsic, and extrinsic patient factors, plasma hydrocodone and metabolites, common side effects, and pain scores in a cohort of orthopedic surgery patients.Data for each patient was collected by review of the electronic hospital record (EHR), and patient interview. Patients were recruited from those with trauma or undergoing scheduled elective surgery for total knee replacement or total hip at the University of Louisville Hospital, Baptist East Hospital, and Jewish Hospital, Louisville, KY. Plasma opiate concentrations and a targeted genotyping panel was performed.There were statistically significant correlations with daily (p 0.001) and total dose (p = 0.002) of hydrocodone in hospital and duration of opioid therapy. The length of opioid administration was significantly shorter in CYP2D6 EM/UM versus CYP2D6 PM/IM patients (p = 0.018). Subjects with the OPRM1 c.118G variant were also on opioids longer (p = 0.022). The effect of co-administration of a CYP2D6 inhibitor had a significant effect on the length of opioid therapy (P 0.001). And not surprisingly the effect of the inhibitor adjusted CYP2D6 phenotype was greater in both the hospital stay period and days of opioid use post hospital discharge (p 0.001).Based on this study, patients should be evaluated for the use of inhibitors of CYP2D6, during hydrocodone therapy can alter the phenotype of the patient (phenocopy) and increase the probability that the patient will be on opioids for longer periods of time.